1. Field of the Invention
The present invention relates to the field of fluidics and, in particular, a liquid-handling apparatus having a liquid switch and a method for handling liquids. More particular, the present invention relates to a liquid-handling apparatus and method in which liquid volumes are driven by the centrifugal force and in which liquid volumes can be routed from a common inlet to one of two outlet channels, into which the inlet channel branches.
2. Description of Prior Art
Rotating disks have been introduced as convenient platforms, which allow flow control based on centrifugal forces, see M. J. Madou and G. J. Kellogg: “LabCD: A centrifuge-based, microfluidic platform for diagnostics”, in Proceedings of SPIE, vol. 3259, 1998, pp 80-93; Michael J. Felton, “CD-based fluidics may offer a simple pumping alternative for lab-on-a-chip systems for some everyday applications”, Analytical Chemistry, Vol. 75, No. 13, Jul. 1, 2003, pp. 302A to 306A; G. Ekstrand et al., “Microfluidics on a rotating CD”, Proceedings of μTAS 2000, Eds. A. van den Berg, W. Olthuis and P. Bergveld; C. T. Schembri et al., “Centrifugation and capillarity integrated into a multiple analyte whole-blood analyzer”, vol. 17, no. 3, ppl 99 to 104, 1995; and D. C. Duffy et al., “Rapid prototyping of microfluidic switches in poly(dimethyl siloxane) and their actuation by electro-osmotic flow”, J. Micromech. Microeng. 9, pp. 211 to 217, 1999.
Centrifugals systems are known from the following companies: Abaxis at www.abaxis.com; Gyros at www.gyros.com; Tecon at www.tecan.com.
The centrifugal force creates an artificial gravity pointing in a radial direction. Flow control on rotating platforms is, for instance, achieved by capillary-burst valves, which are hydrophobic patches blocking a flow until a specific angular speed is reached. So far, the impact of the pseudo Coriolis force has not been considered for those platforms, despite the fact that the Coriolis force can prevail over all other forces beyond a certain speed of rotation.
Making use of the above-mentioned effect to realize a novel flow switch, which is controlled by the Coriolis force, is shown in the article T. Brenner, T. Glatzel, R. Zengerle, J. Ducrée: A Flow Switch Based on Coriolis Force, Proc. μTAS 2003, Oct. 5-9, 2003, Squaw Valley, Calif., USA, 2003, 903-906. The technique described in this article goes back to the inventors of the present invention and was made public on Oct. 5, 2004 for the first time. This article shows a flow switch, which is controlled by the Coriolis force on a centrifugal “lab-on-a-disk” platform (lab=laboratory). The Coriolis switch consists of an inverse Y-structure with one common upstream channel and two symmetric outlets. Above a certain threshold frequency ω0, the Coriolis force becomes dominant to direct nearly 100% of the flow in one of the outlets, which is selected by the direction of rotation. According to this article, the threshold frequency has been measured to be 350 rad s−1 for a channel width of 360 micrometers and a depth of 125 micrometers.
Coriolis-induced switching has been published by the inventors in further publications, see Thilo Brenner, Thomas Glatzel, Roland Zengerle and Jens Ducrée: “Frequency Dependent Transversal Flow Control in Centrifugal Microfluidics”, accepted for publication in Lab on a Chip, 2004; J. Ducrée, T. Glatzel, T. Brenner, R. Zengerle: “Coriolis-Induced Flow Control for Micro- and Nanofluidic Lab-on-a-disk Technologies”, International Forum on Micro & Nano Integration (MINIT), 3-4. December 2003, Potsdam, Germany, 2003, pp. 147-153; J. Ducrée, T. Glatzel, T. Brenner, R. Zengerle: “Coriolis-Induced Flow Control in Centrifugal Microfluidics”, Proc. NanoTech 2003; Nov. 25-27, 2003, Montreux, Switzerland, 2003; and J. Ducrée, T. Brenner, T. Glatzel, R. Zengerle: “Coriolis-Induced Switching and Mixing of Laminar Flows in Rotating Microchannels”, Proc. Micro. Tec 2003, Oct. 14-15, 2003, Munich, Germany, 2003, 397-404.
With respect to the technique of a flow switch based on Coriolis force, the teachings of the above-mentioned publications going back to the inventors of the present invention are introduced herein by reference.
In the field of microbiology, stationary phases are used for extraction, upgrading and purification of substances. Extraction, upgrading and purification of important substances, such as nucleic acids, typically requires a sequence of liquid volumes to be run through a stationary phase, which can be formed by silica particles, for example.
The sequence of liquid volumes comprises a sample buffer, a wash buffer and an elution buffer in this order. Depending on the present chemical conditions, pH, temperature or ionic strength of the solution, for example, the target molecules bind to the stationary phase in a specific manner and, thereafter, solve in purified and an upgraded manner in the elution buffer.
In conventional systems, the liquid volumes are driven through the stationary phase, making use of classical hydrodynamic pumps, the gravity or by centrifugation, so-called “spin columns”. After each step except for the last step, the substances driven through the stationary phase have to be removed from the bottom of the receiving vessel, generally manually in order to provide, in the last step, the pure eluate including the extracted sample. In a routine operation, this method comprising a plurality of steps is very time-consuming, cumbersome and liable to faults, in particular, if a plurality of samples have to be treated.